The proposed treatment schedule consists of a combination of Clofarabine plus Cyclophosphamide administered over 5 consecutive days (Treatment scheme). This is an open, nonrandomized prospective phase II trial aimed to evaluating (1) activity of this combination in terms of CR rate.

- STEP 1. All eligible patients will be screened for the availability of an HLA-matched or partially mismatched compatible HSCT donor, of both family related - or unrelated type (early activation required), including cord blood and haploidentical siblings. Moreover, pre-treatment investigation will include collection and storage of patient ALL cells for specific biological studies relating to sensitivity and response to study chemotherapeutic combination.

- STEP 2. Cycle 1 will be applied to all eligible patients once all enrollment criteria are confirmed.

- STEP 3. After cycle 1, response will be evaluated.

- STEP 4. After remission induction cycle 1, only responsive patients (CR or PR, see below for definitions) could be given cycle 2, according to the opinion of the responsible physician and with a minimum intercycle interval of 4 weeks from day 1 of cycle 1. All NR patients will be declared off study and will not be given a second course with study combination. The suggested treatment following cycle 2 (or cycle 1 if cycle 2 is omitted) is HSCT.

Inclusion Criteria:

- Signed written informed consent according to IGH/EU/GCP and national local laws.

- Age 18-60 years.

- ALL with B-/T-precursor phenotype refractory to first line therapy.

- ALL with B-/T-precursor phenotype 1st isolated bone marrow relapse, occurring < 24 months from the achievement of first CR, after chemotherapy or hematopoietic stem-cell transplantation (HSCT) defined as follows:

* ≥ 5% leukemic blasts in the bone marrow not attributable to another cause (e.g. marrow regeneration); if there are no circulating blasts and the bone marrow contain 5-20% leukemic blasts, a repeat bone marrow performed at least a week later is necessary to confirm relapse.

- Severe neurological or psychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan.

- Active uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).

- Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of Clofarabine-Cyclophosphamide). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs.

Type of Study:

Study Design:

Outcome Measure:

The primary end-point is the rate of patients in CR after induction therapy.

Outcome Description:

Disappearance of any clinical and laboratoristic sign of ALL. The patient must be transfusion-free with neutrophils >1.0 x109/L and platelets >100 x109/L. BM examination must show absence or reduction of blast cell content (< 5%, none of which obviously leukemic), with cellularity in the normal or slightly hypocellular range and with evidence of trilineage hemopoiesis. BM is examined on day 28 from start of chemotherapy cycle 1, or later as clinically indicated in ill/cytopenic patients, and after cycle 2 in patients with PR proceeding to this treatment.

Outcome Time Frame:

At day +28 from start of chemotherapy cycle 1 and after cycle 2 in pts with PR

Safety Issue:

No

Principal Investigator

Renato BASSAN, Pr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

U.O. di Ematologia- Ospedale dell'Angelo - Mestre

Authority:

Italy: Ethics Committee

Study ID:

LAL1610

NCT ID:

NCT01462253

Start Date:

July 2012

Completion Date:

July 2015

Related Keywords:

Acute Lymphoblastic Leukemia

Adult patients

Refractory

Relapsed

clofarabine

cyclophosphamide

refractory and relapsed acute lymphoblastic leukemia

ALL

Leukemia

Leukemia, Lymphoid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

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